Around the world more than thirty million people are infected by the HIV virus. Numerous drugs and combination therapies have been developed for the treatment of HIV infections in humans. While combination antiretroviral therapies (cART) and highly active antiretroviral therapies (HAART) have been able to reduce HIV viral loads, often below 50 copies of HIV RNA/ml of plasma, no therapy has provided elimination of HIV infected cells which are not actively replicating HIV, commonly referred to as a patient's latent reservoir of HIV. “Kick and kill” strategies have been proposed for reservoir reduction and/or elimination. Compounds with “kick” activity have the potential to reverse latency and increase HIV protein expression in infected cells, making them more susceptible to immune-mediated killing. Compounds with “kill” activity have the potential to enhance killing of HIV-infected cells, e.g. by enhancing immune effector cell function. “Kick” programs have tested various agents, including histone deacetylase inhibitors, disulfiram, PD-1 antibodies, and HIV vaccines, as noted in Prospects for Treatment of Latent HIV, Barton et al., Clin. Pharm. & Therap., Vol. 93, Issue 1, pp. 46-56; Neutralizing the HIV Reservoir, Marsden et al., Cell, 158, Aug. 28, 2014, pp. 971-972; HIV-1 Latency: An Update of Molecular Mechanisms and Therapeutic Strategies, Battistini et al., Viruses 2014, 6, 1715-1758; and Quantification of HIV-1 latency reversal in resting CD4+ T cells from patients on suppressive antiretroviral therapy, Cillo et al., PNAS, May 13, 2014, Vol. 111, No. 19, pp. 7078-7083.
There remains a need for new agents and therapies capable of assisting in the activation of the latent HIV-infected cells to enhance the activity of antiretroviral therapies and immune responses.